Abstract: The present disclosure relates to methods of treating EPAS1-related diseases such as cancer, metastases, astrocytoma, bladder cancer, breast cancer, chondrosarcoma, colorectal carcinoma, gastric carcinoma, glioblastoma, head and neck squamous cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, neuroblastoma, non-small cell lung cancer, melanoma, multiple myeloma, ovarian cancer, rectal cancer, renal cancer, clear cell renal cell carcinoma (and metastases of this and other cancers), gingivitis, psoriasis, Kaposi's sarcoma-associated herpesvirus, preeclampsia, inflammation, chronic inflammation, neovascular diseases, and rheumatoid arthritis, using a therapeutically effective amount of a RNAi agent to EPAS1.

Abstract: Methods and compositions for the detection and quantification of nucleic acids are provided. In certain embodiments, methods involve the use of primers or probes that comprise a non-natural nucleotide linked to a reporter. Target nucleic acids are detected by the polymerization of a complementary probe or primer that incorporated a cognate non-natural nucleotide linked to a quencher.

Abstract: Methods, compositions, and kits are provided for CRISPR/Cas mediated transcriptional modulation.

Abstract: This document provides methods and materials for assessing RNA expression. For example, methods and materials for detecting the presence, absence, or amount of target nucleic acid (e.g., target RNA or target cDNA produced from target RNA), kits for detecting the presence, absence, or amount of target nucleic acid (e.g., target RNA or target cDNA produced from target RNA), and methods for making such kits are provided.

Abstract: The invention relates, in part, to systems and methods for scoring a sample containing tumor tissue from a cancer patient. The score is representative of a nearness between at least one pair of cells, a first member of the least one pair of cells expressing a first biomarker and a second member of the at least one pair of cells expressing a second biomarker that is different from the first biomarker. The score obtained from these methods can be indicative of a likelihood that a patient may respond positively to immunotherapy.

Abstract: The present invention is directed to methods for reducing cross-reactivity between species employed in multiplexed immunoassays.

Abstract: CRISPR/CAS-related compositions and methods for treatment of Sickle Cell Disease (SCD) are disclosed.

Abstract: Disclosed are methods of diagnosing and treating metastatic cancer in a subject. The methods involve detecting or modulating the expression of at least one of Kif3b, ACTB, SRPK1, TM EM 229b, Cl4orf142, KB-1460A1.5, ACTC1, Nr2f1, KIAA0922, KDELR3, APBA2, miRNA 130b, miRNA 374b, or miRNA 122 in a biological sample from the subject.

Abstract: The present invention relates to a microfluidic device to manipulate, select, treat, or cultivate living bodies, comprising a first chamber, a second chamber and a network of guiding tracks, wherein: said network of guiding tracks comprises at least one first guiding track connecting the first chamber and the second chamber and at least one second guiding track connecting said at least one first guiding track with at least two interconnections; and said at least one second guiding track comprises a curved part; said curved part exhibiting a concavity facing the second chamber or the part of the network connected to the second chamber.

Abstract: A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Abstract: Provided herein are compositions and methods for detecting the binding of a peptide to an MHC molecule, and the binding of a peptide:MHC complex to a TCR. In preferred embodiments, the compositions and methods are in a highly-multiplexed way. The compositions and methods disclosed herein can be used to provide direct information on which peptides are bound to an MHC molecule. Also provided is a method for simultaneously detecting a large number of peptides for binding to an MHC molecule and/or a T cell. A method for detecting competitive binding of a large number of peptides to an MHC molecule and/or a T cell is also disclosed. Also provided herein is a method for simultaneously detecting a large number of specific TCRs. The compositions and methods of the present invention are useful for vaccine design, research and monitoring of autoimmune and infectious disease, immunogenicity testing of therapeutics, and tissue typing.

Abstract: A method of trapping constituents of interest in a fluid sample flowing through a microfluidic channel by vibrating an interface of the fluid sample and a gas occupying a lateral channel adjacent the microfluidic channel is described. A marker is flowed into the microfluidic channel such that the marker bonds with constituents of interest. The constituents of interest bonded to the marker can help identification of the constituents of interest.

Abstract: The present invention relates to the selection of patients with enhanced antipsychotic treatment efficacy with iloperidone based on a patient's genotype at one or more single nucleotide polymorphism (SNP) loci and to treatment of such patients based upon the identification of their genetic information.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences. In particular, the present invention provides methods and compositions for improving the efficiency of sequencing reactions by using fewer labels to distinguish between nucleotides and by detecting nucleotides at multiple detection positions in a target sequence.

Abstract: The present disclosure provides a Cas9 heterodimer, as well as nucleic acids encoding the Cas9 heterodimer, and host cells comprising the nucleic acids. The present disclosure provides a system that includes a Cas9 heterodimer of the present disclosure and at least one of: a Cas9 guide RNA, and a dimerizing agent. A Cas9 heterodimer of the present disclosure is useful in a wide variety of applications, which are also provided.

Abstract: This disclosure relates to the field of secondary metabolite production in plants. More specifically, the disclosure relates to chimeric genes encoding a bHLH protein of subfamily Iva comprising a bHLH domain and their use in the regulation of biosynthesis and/or production of secondary metabolites in plants and plant-derived cell cultures.

Abstract: The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.

Abstract: The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Abstract: Modulation of microRNAs against myotonic dystrophy type 1 and antagonists of microRNAs therefor. The invention provides the use of inhibitors of microRNAs repressors of MBNL1 and/or MBNL2 genes for the manufacture of a medicinal product for the treatment of myotonic dystrophy 1. Inhibiting these microRNAs allows to increase the endogenous levels of the corresponding proteins MBNL1 and/or MBNL2, thereby alleviating symptoms of the disease, especially when inhibiting repressors that are expressed in the main affected organs: skeletal muscle, heart or organs of the central nervous system. The inhibition of the microRNAs miR-23b-3p and miR-218-5p is preferred. It also provides oligoribonucleotide or oligoribonucleotide analogue antagonists suitable therefor, preferably antagomiRs directed against the microRNAs mentioned with chemical modifications that enhance their interaction with the target, their stability in vivo and their ability to penetrate into the cells and distribute throughout tissues and organs.

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by improved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

Abstract: The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Abstract: A method is provided comprising the following steps: (a) treating a nucleic acid with bisulfite to convert non-methylated cytosines in the nucleic acid into uracils while leaving methylated cytosines unchanged to form a treated nucleic acid strand that is part of two joined nucleic acid strands; (b) ligating a first adapter to a 3? end of the treated nucleic acid strand, the first adapter having a first protruding random sequence that least 3 bases long and that acts as a splint for the two joined nucleic acid strands; (c) ligating a second adapter to a 5? end of the once adapter ligated nucleic acid strand, the second adapter having a second protruding random sequence at least 3 bases long and that acts as a splint for the two joined nucleic acid strands; and (d) performing PCR amplification on the twice ligated nucleic acid strand.

Abstract: The invention provides compositions comprising nucleic acid complexes for use in monitoring binding interactions and in measuring association and/or dissociation kinetics, detecting analytes including low concentration analytes, and screening library members. In some instances, the nucleic acid complexes are double-stranded nicked nucleic acids comprising a scaffold nucleic acid hybridized to one or more oligonucleotides. In some instances, a first, a second, a third, and optionally a fourth oligonucleotide are linked to moieties that are known to interact with each other or which are suspected of interacting with each other or of interacting with a common moiety such as an analyte. Changes in topology of the complex are used to determine the binding interactions of the various binding partners.

Abstract: The present disclosure provides nucleic acid molecules, and kits comprising the same, for producing templated assembly products for a cell.

Abstract: The present invention relates to a biomarker and uses thereof for liver cancer diagnosis or prognosis prediction. The biomarker according to the present invention may be used as a marker for liver cancer diagnosis and prognosis prediction with improved specificity and sensitivity. Thus, the biomarker may be used not only to diagnose or prognose liver cancer with high accuracy and reliability, but also to effectively screen a liver cancer treatment agent.

Abstract: The present invention relates to methods for shifting the splicing profile of the DUX4 gene, a double homeobox gene on human chromosome 4q35. Recombinant adeno-associated viruses of the invention deliver DNAs encoding U7-based small nuclear RNAs to induce DUX4 exon-skipping and the expression of shortened forms of DUX4. The methods have application in the treatment of muscular dystrophies such as facioscapulohumeral muscular dystrophy.

Abstract: A pressure regulator module for a chip-based microfluidic platform is provided. The module includes a microfluidic channel for passing flowable material from the inlet region through the outlet region and into a downstream compartment; one or more microvalves fluidly connected to the microfluidic channel and upstream of the outlet region; and one or more reservoirs fluidly connected to the microvalves, for receiving flowable material diverted by the microvalves, where a flow of flowable material passing from the inlet region toward the downstream compartment is at least partially diverted by the microvalves into the reservoirs as a result of a pressure increase in the microfluidic channel. In some versions, the microvalves are capillary burst valves. A microfluidic chip containing the module and a method of using the module are provided.

Abstract: An electrochemical probe for in-vivo measurement of H2O2 oxidation within a living tissue. The electrochemical probe includes a sensing part and a handle. The sensing part includes a working electrode including a first biocompatible conductive needle, a counter electrode including a second biocompatible conductive needle, and a reference electrode including a third biocompatible conductive needle. The working electrode, the counter electrode, and the reference electrode are configured to be put in contact with the living tissue by inserting the sensing part into the living tissue. The handle includes an insertion part that may be configured to insert the sensing part into the living tissue. The sensing part is attached to the insertion part.

Abstract: An electrochemical system for cancer diagnosis. The electrochemical system includes a sensor configured to be put in contact with a sample suspected to be cancerous, an electrochemical stimulator-analyzer, a processor electrically connected to the electrochemical stimulator-analyzer, and an array of electrically conductive connectors connecting the sensor to the electrochemical stimulator-analyzer.

Abstract: Provided are devices, systems, and methods for the identification, quantification, and profiling of microscopic organisms. The methods for the identification, quantification, and profiling of microscopic organisms include, for example, the selective enrichment of microscopic organisms from a heterogeneous sample; subsequent loading of the microscopic organisms into microfluidic channels or reaction chambers; direct amplification of nucleic acids from single, isolated microscopic organisms; and examination of amplification products using digital High Resolution Melting (HRM) analysis.

Abstract: Disclosed are processes and kits for rapid nucleic acid extraction from a nucleic acid-containing material, such as a bone, tooth or semen sample. For bone and tooth process involves providing the nucleic acid-containing material in a form suitable for nucleic acid extraction, adding a lysis buffer to the nucleic acid-containing material to obtain a mixture, mixing the mixture in a manner equivalent for about 30 seconds or longer and separating the mixture by centrifugation to obtain a liquid supernatant. The liquid supernatant contains the extracted nucleic acids which can be used for analysis including STR profiling by conventional or rapid DNA analysis. For semen the processes and kits involve applying an appropriate amount of sperm disruptive agent.

Abstract: The invention is a novel method of making and using a library such as a sequencing library of single stranded circular nucleic acid templates via splint ligation.

Abstract: Provided herein are materials and methods for efficiently delivering nucleic acids to cochlear and vestibular cells.

Abstract: A composition and method for preserving a urine sample and a preservative delivery vessel are disclosed wherein treatment of the urine sample aids in preserving circulating cell-free nucleic acids in urine over a wide range of dilution ratios within temperature fluctuations that can occur during urine sample handling, storage and transportation. The urine sample preservation composition and method and preservative delivery vessel provide a method for obtaining high quality stabilized urinary cell-free nucleic acids for clinical diagnostics development and application.

Abstract: The present invention provides a method for genomic profiling of DNA 5-methylcytosine and 5-hydroxymethylcytosine, comprising the following steps: (1) DNA purification and fragmentation pretreatment: the target DNA is extracted and then broken to an average of 50 nucleotides to 10,000 nucleotides in length; (2) the repair of trace amount of DNA and the ligation thereof to the adaptor: the pre-treated DNA fragments are repaired and ligated with the sequencing adaptor required for the second-generation sequencing, (3) covalently labeling 5-methylcytosine and 5-hydroxymethylcytosine, (4) solid-phase enrichment of the labeled DNA fragments having cytosine with 5-position modification; (5) the PCR amplification of the solid-phase enriched DNA fragments, the PCR product is obtained and purified to obtain a library for the second-generation sequencing, after mapping the sequencing reads to the genome, the distribution map of the cytosine with 5-position modification in the DNA sample could be generated.

Abstract: The present invention is based on BCR-ABL1 splice variants which result from insertion and/or truncation of the bcr-abl1 transcript and the finding that these variants provide resistance to kinase domain inhibitors such as imatinib, nilotinib and dasatinib.

Abstract: Provided herein are methods of measuring C19MC miRNA amount and/or expression in a post-natal cell and/or tissue. Provided herein are methods of measuring CpG methylation of the upstream C19MC miRNA promoter region in a post-natal cell and/or tissue. Also provided herein are methods of treating a cell, population thereof, and/or a subject in need thereof by administering a C19MC miRNA inhibitor or CRISPR to suppress the expression of specific miRNA within the C19MC or the entire C19MC cluster, population thereof, and/or the subject in need thereof.

Abstract: The invention is a novel method of generating a library of circular single stranded nucleic acid molecules by utilizing circular capture molecules. The method is not limited by size of target nucleic acid molecules and can potentially accommodate very long molecules. The method finds application in nucleic acid sequencing, e.g., nanopore sequencing where unlimited-length templates can be read.

Abstract: This invention relates to the field of ribonucleic acid (RNA) regulation of intracellular activity. In particular, the invention relates to compositions and methods of identifying and tracking specific intracellular RNAs. For example, a fluorescently tagged RNA probe may be tracked by in vivo live imaging throughout its intracellular lifetime in order to determine its purpose and identify regulatory targets to modify its effects. Alternatively, an RNA probe may carry a therapeutic payload for treatment of medical condition or disorder.

Abstract: Provided are systems and methods for analyzing a single cell application or experiment. A set of control beads may be introduced to a biological sample and subjected to the single cell application. The control beads may be configured to mimic analytes in the biological sample, such as a cell or other analyte, and comprise one or more known sequences. The one or more known sequences may be identified to analyze the single cell application.

Abstract: The methods and systems described herein provide an improved emulsion droplet based nucleic acid amplification method, which allows nucleic acids contained in biological systems to be detected, quantitated and/or sorted based on their sequence as detected with nucleic acid amplification techniques, e.g., polymerase chain reaction (PCR). The nucleic acids can be free floating or contained within living or nonliving structures, including particles, viruses, and cells. The nucleic acids can include, e.g., DNA or RNA.

Abstract: This disclosure relates to compositions comprising particles conjugated to one or more catalytically cleaving nucleic acids and optionally an RNA ligating enzyme. In certain embodiments, particles reported herein are used for splicing nucleic acid sequences.

Abstract: Provided herein are methods, compositions, systems, devices, and kits for quantification of RNA, and determination of efficiency of reverse transcription of RNA to cDNA.

Abstract: Gene editing can be performed by introducing gene-editing components into a cell by mechanical cell disruption. Related apparatus, systems, techniques, and articles are also described. The methods and systems of the invention solve the problem of intracellular delivery of gene editing components and gene editing complexes to target cells. The results described herein indicate that delivery of gene editing components, e.g., protein, ribonucleic acid (RNA), and deoxyribonucleic acid (DNA), by mechanical disruption of cell membranes leads to successful gene editing. Because intracellular delivery of gene editing materials is a current challenge, the methods provide a robust mechanism to engineer target cells without the use of potentially harmful viral vectors or electric fields.

Abstract: This invention claims processes that append a single nucleotide having a 3?-ONH2 moiety to the 3?-ends of an oligonucleotide primer using 3?-deoxynucleoside triphosphates that have, instead of a 3?-OH moiety, a 3?-ONH2 moiety, where the nucleotides contain both standard and non-standard nucleobases, and where as a key claim limitation, substantially no hydroxylamine is present in the solutions used in the claimed processes.

Abstract: Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes a survival factor, wherein the genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor.

Abstract: Provided herein is technology for neoplasia screening, and particularly, but not exclusively, to methods, compositions, and related uses for detecting the presence of cancer, in particular, colorectal cancer.

Abstract: The invention generally relates to a molecular classification of disease predisposition and particularly to molecular markers for cancer predisposition and methods of use thereof.

Abstract: A method includes reconstituting a lyophilized microbial community. Ribonucleic acid (RNA) is extracted from at least one targeted microbe in the reconstituted microbial community at a plurality of selected time periods. The RNA as extracted at the selected time period is subjected to a multiplex analyzer and determining RNA concentrations at the plurality of selected time periods. An increase in the RNA concentration from a first of the plurality of selected time periods to a second of the plurality of time periods indicates RNA expression from the at least one targeted microbe. RNA expression from the at least one targeted microbe indicates that the at least one targeted microbe is a living microbe.

Abstract: The invention provides methods for simultaneously amplifying multiple nucleic acid regions of interest in one reaction volume as well as methods for selecting a library of primers for use in such amplification methods. The invention also provides library of primers with desirable characteristics, such as minimal formation of amplified primer dimers or other non-target amplicons.